Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/147355 |
Resumo: | Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022 |
id |
RCAP_19a351ae26bfcea0eee50720d333c17f |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/147355 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiationPossible implications for SARS-CoV-2 impact on brain development3D neurospheresAOPbrain developmentCIAO ProjectElectrical activityRNA-SeqSpike proteinToxin-like peptidesToxicologyFunding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022The possible neurodevelopmental consequences of SARS-CoV-2 infection are presently unknown. In utero exposure to SARS-CoV-2 has been hypothesized to affect the developing brain, possibly disrupting neurodevelopment of children. Spike protein interactors, such as ACE2, have been found expressed in the fetal brain, and could play a role in potential SARS-CoV-2 fetal brain pathogenesis. Apart from the possible direct involvement of SARS-CoV-2 or its specific viral components in the occurrence of neurological and neurodevelopmental manifestations, we recently reported the presence of toxin-like peptides in plasma, urine and fecal samples specifically from COVID-19 patients. In this study, we investigated the possible neurotoxic effects elicited upon 72-hour exposure to human relevant levels of recombinant spike protein, toxin-like peptides found in COVID-19 patients, as well as a combination of both in 3D human iPSC-derived neural stem cells differentiated for either 2 weeks (short-term) or 8 weeks (long-term, 2 weeks in suspension + 6 weeks on MEA) towards neurons/glia. Whole transcriptome and qPCR analysis revealed that spike protein and toxin-like peptides at non-cytotoxic concentrations differentially perturb the expression of SPHK1, ELN, GASK1B, HEY1, UTS2, ACE2 and some neuronal-, glia- and NSC-related genes critical during brain development. Additionally, exposure to spike protein caused a decrease of spontaneous electrical activity after two days in long-term differentiated cultures. The perturbations of these neurodevelopmental endpoints are discussed in the context of recent knowledge about the key events described in Adverse Outcome Pathways relevant to COVID-19, gathered in the context of the CIAO project (https://www.ciao-covid.net/).NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNFrancesca, PistollatoMauro, PetrilloClerbaux, Laure AlixLeoni, GabrielePonti, JessicaBogni, AlessiaBrogna, CarloCristoni, SimoneSanges, RemoMendoza-de Gyves, EmilioFabbri, MarcoQuerci, MaddalenaSoares, HelenaMunoz, AmaliaWhelan, MauriceVan de Eede, Guy2023-01-11T22:16:31Z2022-082022-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15application/pdfhttp://hdl.handle.net/10362/147355eng0890-6238PURE: 44791991https://doi.org/10.1016/j.reprotox.2022.04.011info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:28:26Zoai:run.unl.pt:10362/147355Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:52.972942Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation Possible implications for SARS-CoV-2 impact on brain development |
title |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
spellingShingle |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation Francesca, Pistollato 3D neurospheres AOP brain development CIAO Project Electrical activity RNA-Seq Spike protein Toxin-like peptides Toxicology |
title_short |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
title_full |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
title_fullStr |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
title_full_unstemmed |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
title_sort |
Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation |
author |
Francesca, Pistollato |
author_facet |
Francesca, Pistollato Mauro, Petrillo Clerbaux, Laure Alix Leoni, Gabriele Ponti, Jessica Bogni, Alessia Brogna, Carlo Cristoni, Simone Sanges, Remo Mendoza-de Gyves, Emilio Fabbri, Marco Querci, Maddalena Soares, Helena Munoz, Amalia Whelan, Maurice Van de Eede, Guy |
author_role |
author |
author2 |
Mauro, Petrillo Clerbaux, Laure Alix Leoni, Gabriele Ponti, Jessica Bogni, Alessia Brogna, Carlo Cristoni, Simone Sanges, Remo Mendoza-de Gyves, Emilio Fabbri, Marco Querci, Maddalena Soares, Helena Munoz, Amalia Whelan, Maurice Van de Eede, Guy |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
dc.contributor.author.fl_str_mv |
Francesca, Pistollato Mauro, Petrillo Clerbaux, Laure Alix Leoni, Gabriele Ponti, Jessica Bogni, Alessia Brogna, Carlo Cristoni, Simone Sanges, Remo Mendoza-de Gyves, Emilio Fabbri, Marco Querci, Maddalena Soares, Helena Munoz, Amalia Whelan, Maurice Van de Eede, Guy |
dc.subject.por.fl_str_mv |
3D neurospheres AOP brain development CIAO Project Electrical activity RNA-Seq Spike protein Toxin-like peptides Toxicology |
topic |
3D neurospheres AOP brain development CIAO Project Electrical activity RNA-Seq Spike protein Toxin-like peptides Toxicology |
description |
Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022 |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-08 2022-08-01T00:00:00Z 2023-01-11T22:16:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/147355 |
url |
http://hdl.handle.net/10362/147355 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0890-6238 PURE: 44791991 https://doi.org/10.1016/j.reprotox.2022.04.011 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
15 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799138120070856704 |